We will continue the synthesis and biological evaluations of dopamine receptor agonists. We will continue to develop new synthetic procedures and biological tests. We will incorporate in vivo and in vitro testing for involvement of dopamine receptros in both the central and peripheral nervous system. Assays will be based on peripheral and regional administration of compounds to the caudate nucleus. The experiments will quantify activity for pre- vs postsynaptic sites for both the peripheral and central nervous systems. Metabolism studies will be incorporated to evaluate metabolic activation. Pharmacolinetic studies of selected compounds will be instituted. Some of the major discoveries concerning chemical entities in relation to biological activity that will be explored are summarized as follows: non-hydroxylated compounds are potent dopamine receptor agonists, pro-drugs which are metabolically activated appear to be a reality, defining the active fragment of the ergoline structure offers many biological and synthetic opportunities, and compounds have been described with selective pre- or postsynaptic activity and this new area of research must be expanded. Possible therapeutic applications are several. (1) Short acting inhibitors of sympathetic neuronal transmission for control of acute hypertensive crisis have been discovered. Synthelabo has di n-propyl dopamine in advance toxicology and pharmacological evaluation. (2) The non-hydroxylated inhibitors of sympathetic neuronal hypertension. Long acting, orally effective agents have been discovered. (3) Selective pre-synaptic inhibitors of dopamine neuronal transmission within the central nervous system offer the opportunity to develop neuroleptic agents which differ in their biological properties from the present therapeutic agents. (4) The ability of dopamine agonists to modify behavior is apparent. Possible clinical application awaits research.